Core B: Biostatistics/Epidemiology Core. Molecular and biochemical methods are becoming available to describe the pathway from exposure to disease. Biomarkers offer effective measures of biological exposure including components of duration and intensity. Early biological effects (which may include mutations) may serve to identify individuals for therapeutic interventions. Once biomarkers of cumulative exposure and disease progression are identified, trials can be designed to prevent early effects on those likely to be exposed. Studies such as the one being proposed will provide data to determine whether interventions that modify biomarkers also have an impact on delaying or avoiding the onset of disease. The design, conduct and analysis of the program project require expertise in biostatistics and epidemiology. The specific aims of the Biostatistics/Epidemiology Core are: 1) To establish methods that promote adherence to standard protocols. Given the multi-site nature of the program project, it is essential to establish standard procedures for data collection and management. In particular, the Biostatistics/Epidemiology core will monitor the data entry; will implement data editing procedures and will establish systems for data security and back-up. 2) To collaborate with investigators in the projects of the program for the purpose of study design and data analysis. Data from the studies will require the use of smoothing procedures for graphical representation and the implementation of multivariate regression methods for analyses of longitudinal data and for binary and time to failure outcomes. 3) To develop new statistical methods appropriate for the data generated by the projects which will allow for testing and estimating parameters relevant to the specific aims of the program project.